Q fever

Introduction
Q fever is a zoonotic infection caused by the bacterium Coxiella burnetii, an obligate intracellular Gram-negative organism. It is found worldwide except in New Zealand and Antarctica and can infect a wide range of domestic and wild animals, as well as humans. The disease was first recognized in 1935 in Queensland, Australia—hence the letter “Q” for “query” fever, as the cause was initially unknown.

Q fever can present as an acute self-limiting febrile illness, atypical pneumonia, hepatitis, or as a chronic infection manifesting predominantly as endocarditis. Its ability to persist in the environment for long periods and its low infectious dose make it a notable public health concern.

---

Etiology and Microbiology
Coxiella burnetii is a small, pleomorphic, Gram-negative coccobacillus. It has two antigenic phases:

• Phase I antigen: Highly infectious, found in natural infection.

• Phase II antigen: Result of in vitro passage, associated with the host immune response during acute infection.

The organism exists in two morphological forms:

• Small cell variant (SCV): Highly resistant to environmental stress, enabling survival in dust and soil for months.

• Large cell variant (LCV): Metabolically active and replicates inside host cells.

---

Reservoirs and Transmission
The primary reservoirs are domestic ruminants such as cattle, sheep, and goats. Other animals, including cats, dogs, and wildlife, can also carry the bacterium.

Transmission to humans occurs mainly via:

• Inhalation of contaminated aerosols from animal waste, birth products, or soil.

• Contact with contaminated clothing, wool, or animal bedding.

• Ingestion of unpasteurized milk or dairy products (less common).

• Rarely, human-to-human transmission (e.g., during obstetric exposure).

Due to its high environmental resistance and ability to be aerosolized, C. burnetii is considered a potential bioterrorism agent.

---

Pathogenesis
After inhalation, C. burnetii infects alveolar macrophages and other host cells. It survives and replicates within the acidic environment of the phagolysosome. The organism triggers both humoral and cell-mediated immune responses, with the latter being crucial for bacterial clearance.

The infection may remain asymptomatic, cause acute illness, or progress to chronic disease, depending on host factors such as immune competence and underlying comorbidities.

---

Clinical Manifestations

1. Acute Q Fever
Incubation period: 2–3 weeks (range 9–39 days).

• Fever: Abrupt onset, high-grade, often with rigors.

• Constitutional symptoms: Fatigue, myalgia, headache (often severe and retro-orbital).

• Respiratory symptoms: Dry cough, pleuritic chest pain; atypical pneumonia may develop.

• Hepatic involvement: Elevated liver enzymes; some patients develop hepatitis with hepatomegaly and jaundice.

• Skin rash: Uncommon.

Acute Q fever is self-limiting in many cases but can lead to complications such as myocarditis, pericarditis, or meningoencephalitis.

2. Chronic Q Fever
Occurs in <5% of infected individuals, often months to years after initial infection.
Risk factors: pre-existing valvular heart disease, vascular grafts, immunosuppression, pregnancy.

• Endocarditis: The most common chronic form, often culture-negative, presenting with fever, weight loss, and heart failure signs.

• Vascular infections: Aneurysms, prosthetic graft infections.

• Chronic hepatitis: Rare, often in immunocompromised patients.

---

Diagnosis

1. Clinical Suspicion
Consider in patients with prolonged febrile illness, atypical pneumonia, or hepatitis, particularly with occupational or environmental exposure to livestock.

2. Laboratory Investigations

• Serology (gold standard): Indirect immunofluorescence assay (IFA) detecting IgM and IgG to Phase I and Phase II antigens.

  • Acute infection: High IgG and IgM to Phase II antigens.

  • Chronic infection: High IgG to Phase I antigens.

• Polymerase Chain Reaction (PCR): Detects C. burnetii DNA, useful in early infection before antibody development.

• Liver function tests: May show elevated transaminases in acute hepatitis form.

• Blood cultures: Usually negative.

---

Treatment

1. Acute Q Fever

• First-line antibiotic:

  • Doxycycline (generic name: doxycycline)

    • Adult dose: 100 mg orally twice daily for 14 days.

    • Pediatric dose (≥8 years): 2.2 mg/kg orally twice daily (max 100 mg per dose) for 14 days.

• Pregnant women:

  • Trimethoprim-sulfamethoxazole (generic names: trimethoprim and sulfamethoxazole)

    • Dose: One double-strength tablet (160 mg TMP/800 mg SMX) orally twice daily, continued until delivery (to prevent fetal complications).

2. Chronic Q Fever

• Endocarditis or vascular infection:

  • Combination therapy:

    • Doxycycline (100 mg orally twice daily) plus

    • Hydroxychloroquine (generic name: hydroxychloroquine) 200 mg orally three times daily.

  • Duration: At least 18 months for native valves, ≥24 months for prosthetic valves.

  • Hydroxychloroquine alkalinizes the phagolysosome, enhancing doxycycline activity.

  • Monitor for drug toxicity (ocular toxicity with hydroxychloroquine; gastrointestinal effects with doxycycline).

---

Prevention

1. Non-Pharmacologic Measures

• Avoid contact with birthing animals and contaminated materials.

• Use personal protective equipment (PPE) in high-risk occupations.

• Ensure proper disposal of animal birth products.

• Pasteurize milk and dairy products.

2. Vaccination

• A formalin-inactivated whole-cell vaccine is available in some countries (e.g., Australia) for high-risk occupational groups (abattoir workers, farmers, veterinarians).

• Requires pre-vaccination screening with serology and skin testing to avoid severe hypersensitivity reactions in previously exposed individuals.

---

Prognosis

• Acute Q fever generally has an excellent prognosis with appropriate treatment, with most patients recovering fully.

• Chronic Q fever has a guarded prognosis and requires prolonged combination therapy; untreated cases can lead to death from heart failure or uncontrolled vascular infection.